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Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells

BACKGROUND: During early pregnancy, tolerance of the semi-allogeneic fetus necessitates comprehensive modifications of the maternal immune system. How decidual CD8(+)T (CD8(+)dT) cells balance maternal tolerance of the fetus with defense from invading pathogens remains undefined. METHODS: We investi...

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Detalles Bibliográficos
Autores principales: Liu, Lu, Huang, Xixi, Xu, Chunfang, Chen, Chunqin, Zhao, Weijie, Li, Dajin, Li, Liping, Wang, Li, Du, Meirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268777/
https://www.ncbi.nlm.nih.gov/pubmed/32487187
http://dx.doi.org/10.1186/s12967-020-02371-3
Descripción
Sumario:BACKGROUND: During early pregnancy, tolerance of the semi-allogeneic fetus necessitates comprehensive modifications of the maternal immune system. How decidual CD8(+)T (CD8(+)dT) cells balance maternal tolerance of the fetus with defense from invading pathogens remains undefined. METHODS: We investigated the distribution patterns of CD8(+)T cells and their heterogeneity in paired peripheral blood and decidual tissue in the first trimester of pregnancy using flow cytometry and mRNA-Seq. Gene Set Enrichment Analysis was utilized to determine the transcriptional features of CD8(+)dT cells. Moreover, we examined activation of T cells when they were cocultured with trophoblasts, in addition to the effect of the fetal–maternal environment on peripheral CD8(+)T (CD8(+)pT) cells. RESULTS: We found that, compared with CD8(+)pT cells, CD8(+)dT cells consisted mainly of effector memory cells (T(EM)) and terminally differentiated effector memory cells (T(EMRA)). Both T(EM) and T(EMRA) subsets contained increased numbers of CD27(+)CD28(−) cells, which have been shown to possess only partial effector functions. In-depth analysis of the gene-expression profiles of CD8(+)dT cells revealed significant enrichment in T cell exhaustion-related genes and core tissue residency signature genes that have been found recently to be shared by tissue resident memory cells and tumor(−)infiltrating lymphocytes (TILs). In accordance with gene expression, protein levels of the exhaustion-related molecules PD-1 and CD39 and the tissue resident molecules CD103 and CXCR3 were increased significantly with almost no perforin secretion in CD8(+)dT cells compared with CD8(+)pT cells. However, the levels of granzyme B, IFN-γ, and IL-4 in CD8(+)dT cells were increased significantly compared with those in CD8(+)pT cells. Both CD8(+)dT and CD8(+)pT cells were not activated after being cocultured with autologous trophoblast cells. Moreover, the production of granzyme B in CD103(+)CD8(+)dT cells decreased significantly compared with that in their CD103(−) counterparts. Coculture with decidual stromal cells and trophoblasts upregulated CD103 expression significantly in CD8(+)pT cells. CONCLUSIONS: Our findings indicate that the selective silencing of effector functions of resident CD8(+)dT cells may favor maternal–fetal tolerance and that the decidual microenvironment plays an important role in promoting the residency of CD8(+)T cells and their tolerance–defense balance.